Behavioral Genetics of the Depression/Cancer Correlation: A Look at the Ras Oncogene Family and the ‘Cerebral Diabetes Paradigm’

Abstract

This study investigates the causes of the observed linkage between depression and later onset of cancer. The prevailing view is that cancer in depressed patients results from a weakened immune system. However, molecular biologists have recognized that dysregulation of the ras proto-oncogene results in impaired serotonin and dopamine synthesis manifesting as major depression. A qualitative review of the literature showed that (1) studies using the Minnesota Multiphasic Personality Inventory showed a greater correlation between depression and later cancer onset than those employing other measures and (2) the more related the cancer type was to the Ras oncogene family, the greater the correlation between depression and later cancer onset. These results support the hypothesis that the ras proto-oncogene plays a role in the etiology of depression and could be the common denominator in long-observed depression/cancer linkages. Previous depression/cancer linkage studies are confounded in that they failed to analyze cancer type and accurately diagnose depression.

Depression and cancer risk: 24 years of follow-up of the Baltimore Epidemiologic Catchment Area sample

“…Another limitation relates to misspecification of the risk model. There might still be other important confounders not accounted for, such as genetic predispositions or innate, unmeasured psychological traits [21, 23]. A third limitation relates to measurement of our exposure variable of depression.…”

“…With respect to genetic theories, we found no empirical evidence to support the hypothesis that ras proto-oncogenes are responsible for the association between depression and cancer. This theory predicts that subtypes of cancer most associated with these oncogenes, specifically skin and lung cancers, should be significantly associated with depression more than other types of cancer, and prostate and breast cancers should be least associated [23]. This was not found.…”

“…More recently, genetic characteristics have been proposed that might lead to both depression and certain subtypes cancer. For example, dysregulated proto-oncogenes of the ras family, which are proteins that direct cell growth, can inhibit dopamine and serotonin synthesis, thereby leading to depression [23–26]. Certain cancers, specifically of the pancreas, lung, colon, and skin, have been associated with disruption of this oncogene family [23].…”

“…Existing prospective cohort studies have several limitations that have been cited as potential sources of null or conflicting findings [13, 23]. Limitations include relatively short follow-up times, with most studies having between 10 and 15 years of prospective follow-up; incomplete or unreliable ascertainment of depression status at baseline; and a lack of proper statistical control of potential confounders.…”

Population Sciences, Translational Research, and the Opportunities and Challenges for Genomics to Reduce the Burden of Cancer in the 21st Century

“…In behavioral science, there is an evolving literature at the intersection of behavior, genes and cancer. For example, there have been suggestions that dysregulation in the ras proto-oncogene might play a role in the observed association between depression and later onset of cancer (42). In T3 research, there is a rich literature on the psychosocial factors relevant to counseling for BRCA1 and treatment decisions (e.g.…”